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Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis

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World Journal of Gastroenterology 2023年第6期29卷 967-996页

作者： Ryutaro Kuraji Takahiko shiba tien s dong Yukihiro Numabe Yvonne L Kapila Department of Periodontology The Nippon Dental University School of Life Dentistry at TokyoTokyo 102-0071Japan Department of Orofacial sciences University of California San FranciscoSan FranciscoCA 94143United States Department of Oral Medicine Infectionand ImmunityHarvard School of Dental MedicineBostonMA 02115United States Department of Periodontology Tokyo Medical and Dental UniversityTokyo 113-8549Japan The Vatche and Tamar Manoukian Division of Digestive Diseases University of California Los AngelesDepartment of MedicineUniversity of California David Geffen School of MedicineLos AngelesCA 90095United States Department of Periodontology The Nippon Dental University School of Life Dentistry at TokyoTokyo 102-8159Japan sections of Biosystems and Function and Periodontics Professor and Associate Dean of ResearchFelix and Mildred Yip Endowed Chair in DentistryUniversity of California Los AngelesLos AngelesCA 90095United States

A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NAsH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NAsH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of N

关键词： Periodontal disease Nonalcoholic fatty liver disease Microbiota Dysbiosis Metabolic syndrome Probiotics

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Impact of sustained virologic response on chronic kidney disease progression in hepatitis C

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World Journal of Hepatology 2017年第36期9卷 1352-1360页

作者： Elizabeth s Aby tien s dong Jenna Kawamoto Joseph R Pisegna Jihane N Benhammou Division of Gastroenterology Hepatology and Parenteral Nutrition Department of Medicine VA Greater Los Angeles Healthcare System the Vatche and Tamar Manoukian Division of Digestive Diseases UCLA Los Angeles Department of Medicine University of California David Geffen School of Medicine

AIM To determine how sustained virological response at 12 wk(sVR12) with direct acting antivirals(DAAs) for the treatment of hepatitis C virus(HCV) infection affects chronic kidney disease(CKD) progression. METHODs A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare system from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between sVR12 subgroups adjusting for co-variates.REsULTs Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate(e GFR) one-year after HCV treatment to one-year before treatment, patients who achieved sVR12 had a decline in GFR of 3.1 m L/min ± 0.75 m L/min per 1.73 m^2 compared to a decline in e GFR of 11.0 m L/min ± 2.81 m L/min per 1.73 m^2 in patients who did not achieve sVR12(P = 0.002). There were no significant clinical differences between patients who achieved sVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in e GFR in those with untreated HCV over 2 years was 2.8 m L/min ± 1.0 m L/min per 1.73 m^2, which was not significantly different from the e GFR decline noted in HCV-treated patients who achieved sVR12(P = 0.43).CONCLUsION Patients who achieve sVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.

关键词： Hepatitis C Direct-acting antivirals Chronic kidney disease End stage renal disease sustained virological response

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Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c

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World Journal of Hepatology 2018年第9期10卷 612-621页

作者： tien s dong Elizabeth s Aby Jihane N Benhammou Jenna Kawamoto steven-Huy Han Folasade P May Joseph R Pisegna the Vatche and Tamar Manoukian Division of Digestive Diseases University of California Los AngelesDepartment of MedicineUniversity of California David Geffen School of MedicineLos AngelesCA 90095United States Division of Gastroenterology Hepatology and Parenteral NutritionDepartment of MedicineVA Greater Los Angeles Healthcare SystemLos AngelesCA 90073United States the Pfleger Liver Institute Department of SurgeryUniversity of California David Geffen School of MedicineLos AngelesCA 90095United States VA Health services Research and Development Center for the study of Healthcare Innovation Center for the study of Healthcare Innovation Implementation and Policy(CSHIIP)Los AngelesCA 90073United States Jonsson Comprehensive Cancer Center Los AngelesCA 90095United States

AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(sVR).METHODs We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the VA Greater Los Angeles Healthcare system treated with varying DAA therapy between 2014-2016. separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of sVR 12-wk post treatment(sVR12).REsULTs A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect sVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved sVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved sVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved sVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve sVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUsION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect sVR12 rates in patients treated with DAA.

关键词： Hepatitis C virus Hemoglobin A1c Diabetes mellitus Direct-acting antivirals Metabolic syndrome

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Data-Driven Learning Control Algorithms for Unachievable Tracking Problems

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IEEE/CAA Journal of Automatica sinica 2024年第1期11卷 205-218页

作者： Zeyi Zhang Hao Jiang dong shen samer s.saab the school of Mathematics Renmin University of ChinaBeijing 100872China IEEE the school of Engineering Lebanese American UniversityByblos 2038Lebanon

For unachievable tracking problems, where the system output cannot precisely track a given reference, achieving the best possible approximation for the reference trajectory becomes the objective. This study aims to investigate solutions using the Ptype learning control scheme. Initially, we demonstrate the necessity of gradient information for achieving the best approximation.subsequently, we propose an input-output-driven learning gain design to handle the imprecise gradients of a class of uncertain systems. However, it is discovered that the desired performance may not be attainable when faced with incomplete information.To address this issue, an extended iterative learning control scheme is introduced. In this scheme, the tracking errors are modified through output data sampling, which incorporates lowmemory footprints and offers flexibility in learning gain design.The input sequence is shown to converge towards the desired input, resulting in an output that is closest to the given reference in the least square sense. Numerical simulations are provided to validate the theoretical findings.

关键词： Data-driven algorithms incomplete information iterative learning control gradient information unachievable problems

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Internal Polarization Field Induced Hydroxyl spillover Effect for Industrial Water splitting Electrolyzers

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Nano-Micro Letters 2024年第2期16卷 438-449页

作者： Jingyi Xie Fuli Wang Yanan Zhou Yiwen dong Yongming Chai Bin dong state Key Laboratory of Heavy Oil Processing College of Chemistry and Chemical EngineeringChina University of Petroleum(East China)Qingdao 266580People’s Republic of China

The formation of multiple oxygen intermediates supporting efficient oxygen evolution reaction(OER)are affinitive with hydroxyl adsorption.However,ability of the catalyst to capture hydroxyl and maintain the continuous supply at active sits remains a tremendous challenge.Herein,an affordable Ni2P/FeP2 heterostructure is presented to form the internal polarization field(IPF),arising hydroxyl spillover(HOso)during OER.Facilitated by IPF,the oriented HOso from FeP2 to Ni2P can activate the Ni site with a new hydroxyl transmission channel and build the optimized reaction path of oxygen intermediates for lower adsorption energy,boosting the OER activity(242 mV vs.RHE at 100 mA cm-2)for least 100 h.More interestingly,for the anion exchange membrane water electrolyzer(AEMWE)with low concentration electrolyte,the advantage of HOso effect is significantly amplified,delivering 1 A cm^(-2)at a low cell voltage of 1.88 V with excellent stability for over 50 h.

关键词： Hydroxyl spillover effect Internal polarization field Heterostructure Oxygen reduction reaction Anion exchange membrane water electrolysis

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Microglial Calcium Homeostasis Modulator 2:Novel Anti-neuroinflammation Target for the Treatment of Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第4期40卷 553-556页

作者： Yuan dong Li Tang Neuropsychiatry Research Institute The Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao266000China Qingdao Institute of Measurement Technology Qingdao266000China

Neurodegenerative diseases,including Alzheimer's disease(AD)and Parkinson's disease(PD),are the most common causes of dementia.Current drugs for such diseases can only provide temporary help with the symptoms,leaving the discovery of new drugs urgently in need.Microglial cells are the local immune cells in the nervous system and have been recognized as the key player in neuroinflammation that contributes to the process of neurodegeneration[1],raising the discussion of aiming microglia as the therapeutic target for clinical treatment of neurodegenerative diseases.

关键词： inflammation degenerative drugs

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Modeling urban scale human mobility through big data analysis and machinelearning

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Building simulation 2024年第1期17卷 3-21页

作者： Yapan Liu Bing dong Department of Mechanical&Aerospace Engineering Syracuse University263 Link HallSyracuseNY 13244USA

In the United states,the buildings sector consumes about 76%of electricity use and 40% of all primary energy use and associated greenhouse gas emissions.Occupant behavior has drawn increasing research interests due to its impacts on the building energy consumption.However,occupant behavior study at urban scale remains a challenge,and very limited studies have been conducted.As an effort to couple big data analysis with human mobility modeling,this study has explored urban scale human mobility utilizing three months Global Positioning system(GPs)data of 93,o00 users at Phoenix Metropolitan Area.This research extracted stay points from raw data,and identified users'home,work,and other locations by Density-Based spatial Clustering algorithm.Then,daily mobility patterns were constructed using different types of locations.We propose a novel approach to predict urban scale daily human mobility patterns with 12-hour prediction horizon,using Long short-Term Memory(LsTM)neural network model.Results shows the developed models achieved around 85%average accuracy and about 86%mean precision.The developed models can be further applied to analyze urban scale occupant behavior,building energy demand and flexibility,and contributed to urban planning.

关键词： urban human mobility big data analysis urban scale occupant behavior recurrent neural networks

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Current understanding of ELF4 deficiency:a novel inborn error of immunity

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World Journal of Pediatrics 2024年第5期20卷 444-450页

作者： Hong-Qiang Du Xiao-dong Zhao Department of Rheumatology&Immunology National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Rare Diseases in Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityZhongshan Er Road 136Yuzhong DistrictChongqingChina

Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited worldwide.As such,our current knowledge of this new disease remains preliminary.This review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel IEI.Data sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency.Our search strategy was“ELF4 OR ETs-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript submission.Results The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric males.In some cases,immunodeficiency and autoimmunity can also be prominent.Targeted sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene.Western blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the variant.To fully confirm the pathogenicity of the variant,further functional test is strongly advised.Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder.Conclusions Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX.When atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function.Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.

关键词： ELF4 transcription factor Immune dysregulation Inborn errors of immunity Mechanism Recurrent infections

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A Long-Time-step-Permitting Tracer Transport Model on the Regular Latitude–Longitude Grid

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Advances in Atmospheric sciences 2024年第3期41卷 493-508页

作者： Jianghao LI Li dong Key Laboratory of Earth system Modeling and Prediction China Meteorological AdministrationBeijing 100081China state key Laboratory of Numerical Modeling for Atmospheric sciences and Geophysical Fluid Dynamics(LAsG) Institute of Atmospheric Physics(IAP)Chinese Academy of SciencesBeijing 100029China state Key Laboratory of severe Weather(LasW) Chinese Academy of Meteorological SciencesChina Meteorological AdministrationBeijing 100081China College of Earth and Planetary sciences University of Chinese Academy of SciencesBeijing 100049China

If an explicit time scheme is used in a numerical model, the size of the integration time step is typically limited by the spatial resolution. This study develops a regular latitude–longitude grid-based global three-dimensional tracer transport model that is computationally stable at large time-step sizes. The tracer model employs a finite-volume flux-form semiLagrangian transport scheme in the horizontal and an adaptively implicit algorithm in the vertical. The horizontal and vertical solvers are coupled via a straightforward operator-splitting technique. Both the finite-volume scheme's onedimensional slope-limiter and the adaptively implicit vertical solver's first-order upwind scheme enforce monotonicity. The tracer model permits a large time-step size and is inherently conservative and monotonic. Idealized advection test cases demonstrate that the three-dimensional transport model performs very well in terms of accuracy, stability, and efficiency. It is possible to use this robust transport model in a global atmospheric dynamical core.

关键词： tracer transport numerical stability latitude–longitude grid

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Cancer cachexia:Focus on cachexia factors and inter-organ communication

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Chinese Medical Journal 2024年第1期137卷 44-62页

作者： Yongfei Wang Zikai dong Ziyi An Weilin Jin The First Clinical Medical College of Lanzhou University LanzhouGansu 730000China Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhouGansu 730000China

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia.Cancer cachexia factors are also a potential target for the diagnosis and treatment.The pathogenesis of cachexia is unclear and no clear effective treatment is available.Thus,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed.From the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment.This review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors.This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

关键词： Cancer cachexia Cancer cachexia factors Inter-organ communication Tumor ecosystem Tumor microenvironment

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